Many steroid hormones exhibit their action upon binding to a receptor in the molecular form secreted from the producing organ, but in the case of male hormones called androgens, for example testosterone enters into cells of the target organ and is reduced to 5α-dihydrotestosterone (5α-DHT) by testosterone 5α-reductase, and the 5α-DHT binds to a receptor and exhibits action as an androgen.
Androgens are important hormones, but if androgens act excessively, then various undesirable symptoms are brought about such as male pattern alopecia, hypertrichosis, seborrhea, acne (pimples etc.), benign prostatic hypertrophy, prostatic tumor, and boy's sexual precocity. Methods for inhibiting the effect of excessive androgens, conventionally resorted to with a view of ameliorating the above symptoms include, specifically, methods for inhibiting the generation of active 5α-DHT by inhibiting the action of testosterone 5α-reductase that reduces testosterone to active 5α-DHT. Known herbal medicines having such testosterone 5α-reductase inhibiting action include, for instance, extracts from plants belonging to the Choerospondias genus (Patent Document 1), extracts from Majito and/or Kachua (Patent Document 2), extracts from starfruit (Patent Document 3), and extracts from one or two or more plants selected from the group consisting of Taxus chinensis, Canarium pimela, Heteropanax fragrans and Andrographis paniculata (Patent Document 4).
Hair grows and falls out repeatedly in accordance with a periodical hair cycle (hair growth cycle) that comprises an anagen stage, a catagen stage and a telogen stage. Within this cycle, the stage that extends from the telogen stage to the anagen stage, when new hair follicles are formed, is believed to be the most important stage in hair growth. Herein, hair papilla cells appear to play an important role in the proliferation and differentiation of hair follicle epithelial cells that take place during this stage. Hair papilla cells, which occur on the inner side of hair follicle epithelial cells comprising outer root sheath cells and matrix cells found in the vicinity of hair roots, are cells located at the root stem portion of the hair root, enveloped by a basal membrane. Hair papilla cells play an important role in the proliferation/differentiation of hair follicle epithelial cells and hair formation, for instance by acting on the hair follicle epithelial cells to promote their proliferation (Non-Patent Document 1).
Since hair papilla cells play an important role in the proliferation/differentiation of follicular epithelial cells and hair formation, alopecia may arguably be prevented/ameliorated by promoting the proliferation of hair papilla cells. Known herbal medicines having hair papilla cell growth action include, for instance, extracts from Astragali Radix, extracts from Coptis japonica and extracts from Wedelia chinensis (Patent Documents 5 and 6).
Fibroblast growth factors (FGFs) are multifunctional secreted factors that, in addition to having proliferative activity towards fibroblasts, play important roles, for instance, as morphogenetic factors having cell proliferation/differentiation activity towards various cells, as tissue repair factors that become active during tissue damage, and as metabolism-regulating factors for supporting organism homeostasis. Examples of FGFs include, for instance, FGF-7. In male pattern alopecia, FGF-7 is known to have a low expression level in hair papilla cells (Non-Patent Document 2). Thus, promoting the production of FGF-7 may arguably allow preventing/ameliorating alopecia and the like. Known natural drugs having such FGF-7 production promoting action include, for instance, royal jelly and the like (Patent Document 7).
As is known, the number of capillaries dramatically decreases around the hair root and in hair papilla cells during the telogen stage, when hair growth stops. By contrast, during the anagen stage, when hair is growing, numerous capillaries are formed anew around the hair root and in hair papilla cells. Neoangiogenesis, therefore, appears to be closely linked to, among others, hair growth and development.
As is known, vascular endothelial growth factor (VEGF), discovered in cultures of pituitary gland follicular cells, is a glycoprotein having a molecular weight of 34 to 46 kDa that acts as a specific growth factor for vascular endothelial cells. VEGF is identical to vascular permeability factor (VPF). In addition to pituitary cells, VEGF is produced also by hair papilla cells. The VEGF thus produced has an angiogenic action whereby it acts on vascular endothelial cells, promoting actions of the proliferation and migration of vascular endothelial cells. Thus, promoting the production of VEGF may arguably allow preventing/ameliorating alopecia and the like. Known plant extracts having VEGF production promoting action include, for instance, plants of the Evolvulus genus, family Convolvulaceae (Patent Document 8).
Bone morphogenetic protein (BMP) is a protein that forms bone, cartilage, tendon as well as other tissues that are present in bone. This protein, which has a specific inducing activity, exists in bone, and hence it has been suggested that it may be an important regulatory factor in bone repair processes, being also involved in normal maintenance of bone tissues. Numerous such proteins are known, and they are classified into various subfamilies (Non-Patent Document 3). An example of BMP is, for instance, BMP-2. The involvement of BMP-2 in hair follicle formation has been pointed out recently, which has drawn interest into the hair-growth action of BMP-2 (Patent Document 9).
[Patent Document 1] Japanese Unexamined Patent Application Laid-open No. 2003-55162
[Patent Document 2] Japanese Unexamined Patent Application Laid-open No. 2002-241297
[Patent Document 3] Japanese Unexamined Patent Application Laid-open No. 2002-241296
[Patent Document 4] Japanese Unexamined Patent Application Laid-open No. 2002-87976
[Patent Document 5] Japanese Unexamined Patent Application Laid-open No. H09-208431
[Patent Document 6] Japanese Unexamined Patent Application Laid-open No. H11-12134
[Patent Document 7] Japanese Unexamined Patent Application Laid-open No. 2003-192541
[Patent Document 8] Japanese Unexamined Patent Application Laid-open No. 2003-160503
[Patent Document 9] Japanese Unexamined Patent Application Laid-open No. 2005-2068
[Non-Patent Document 1] “Trends Genet”, 1992, vol. 8, p. 56-61
[Non-Patent Document 2] “Antiaging Series No. 1 Hair graying, loss and growth in practice” NTS Inc., 2005, p. 91-104
[Non-Patent Document 3] Reddi A. H., “Cytokine Growth Factor Reviews 8”, 1997, p. 11-20